A Trial of Neuroprotection With ACTH in Acute Optic Neuritis

• Status: Active, not recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

We hypothesize that the novel melanocortin-mediated anti-inflammatory effects of ACTH will reduce axonal loss following ON by limiting inflammatory optic nerve injury. We will compare the effect of ACTH and intravenous methylprednisolone therapy on axonal injury following ON using OCT, a sensitive, reproducible and noninvasive tool to measure RNFL thickness.

The primary outcome will be the average RNFL thickness at 6 months. Additional pre-specified statistical analyses will compare the difference in the mean RNFL thickness at 6 months in the affected eye between the IV methylprednisolone- and Acthar-treated groups, and the mean 6-month affected eye RNFL thicknesses adjusted for the baseline unaffected eye RNFL. The secondary outcome measure will examine the frequency of optic nerves with RNFL swelling between the IV methylprednisolone- and Acthar-treated groups at 1 and 3 months. A predefined exploratory outcome will compare the ganglion cell plus inner plexiform layer (GC+IPL) thickness at 6 months between treatment groups. Additional tertiary outcome will be the assessment of changes in fatigue, mood, visual function depression, and quality of life in patients with AON. Assessment will be completed by administration of the following questionnaires: Modified Fatigue Impact Scale, Multiple Sclerosis Quality of Life 54 Instrument, 25-item Visual Function Questionnaire with 10-item supplement, Beck's Depression Inventory. These questionnaires have been validated for the MS (AON) population. Descriptive and correlative analysis will be done at each visit time point to assess for QOL for this study population.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Elliot Frohman; University of Colorado, Denver
• Collaborators: Mallinckrodt; University of Colorado, Denver; University of Pennsylvania
• Treatments: Adrenocorticotropic Hormone; Methylprednisolone; Methylprednisolone Acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate

Criteria

Inclusion criteria

1. Ability to provide written informed consent before any study assessment is performed.

2. Male and female patients aged between 18 and 55 years, inclusive.

3. Diagnosis of clinically unilateral acute demyelinating optic neuritis (ADON)

4. Clinical signs and symptoms of ADON starting within the 14 day prior to intended randomization (loss of vision, pain on movement, impairment of color vision).

5. The qualifying episode of optic neuritis must be the first clinical episode of optic neuritis in the affected eye.

6. Able to undergo treatment with intravenous methylprednisolone or Acthar gel.

Exclusion Criteria:

1. Functionally or clinically relevant comorbidity of the affected eye (e.g., glaucoma, amblyopia, optic nerve hypoplasia, macular hole, macular edema, vitreomacular traction, uveitis, diabetes, optic neuritis, or other diseases of the optic nerve or a history thereof).

2. Bilateral optic neuritis.

3. Concurrent functionally or clinically relevant disturbances of the eye not affected by ADON.

4. High clinical likelihood of a form of optic neuritis other than ADON (e.g., no pain on movement, no light perception, severe optic disk edema, atrophic optic disk, retinal exudates, or hemorrhages).

5. Non-assessable OCT at screening.

6. Refractive error greater than ±5 diopters or (pre-surgical value to be used for patients having undergone refractive surgery).

7. Patients with an immune system disorder other than MS or ADON (e.g. rheumatoid arthritis, scleroderma, Sjogren's syndrome, Crohn's disease, ulcerative colitis, etc.) or with a known immunodeficiency syndrome (AIDS, hereditary immune deficiency, drug-induced immune deficiency). Diagnosis of neuromyelitis optica or MOG-IgG will not exclude a patient from the study but will be accounted for in the data analysis.

8. Prior treatment with IVMP or Acthar gel within the past 30 days.

9. Treatment with, mitoxantrone, cyclophosphamide, mycophenolate, azathioprine, or other non-approved agents for the treatment of relapsing forms of MS.

10. Concurrent use of 4-aminopyridine.